TY - JOUR
T1 - The therapeutic potential of agents targeting the type I insulin-like growth factor receptor
AU - Zhang, Hua
AU - Yee, Douglas
PY - 2004/12
Y1 - 2004/12
N2 - The type I insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase that mediates insulin-like growth factor I (IGF-1) and IGF-2 signalling. Increased expression levels and/or enhanced activity of IGF-1R have been observed in many types of cancer. It is well documented that IGF-1R plays important roles in the proliferation, transformation, motility and metastasis of cancer cells. Therefore, IGF-1R has surfaced as an attractive target for cancer therapy. There are several aspects of this receptor that need to be considered when thinking about inhibitory strategies. In this review, several points relevant to targeting IGF-1R will be discussed, including the signalling pathways downstream of the receptor, the potential role for the insulin receptor in regulating IGF action and multiple cancer phenotypes regulated by this receptor. In addition, there are several strategies that could be used to inhibit IGF action. Inhibition of receptor function by lowering protein expression, decreasing kinase activity by small-molecule inhibitors, disrupting receptor function by monoclonal antibody blockade and neutralising circulating ligand all represent potential therapeutic strategies. As these strategies move forward to clinical trial, several important considerations need to be incorporated into the clinical trial design.
AB - The type I insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase that mediates insulin-like growth factor I (IGF-1) and IGF-2 signalling. Increased expression levels and/or enhanced activity of IGF-1R have been observed in many types of cancer. It is well documented that IGF-1R plays important roles in the proliferation, transformation, motility and metastasis of cancer cells. Therefore, IGF-1R has surfaced as an attractive target for cancer therapy. There are several aspects of this receptor that need to be considered when thinking about inhibitory strategies. In this review, several points relevant to targeting IGF-1R will be discussed, including the signalling pathways downstream of the receptor, the potential role for the insulin receptor in regulating IGF action and multiple cancer phenotypes regulated by this receptor. In addition, there are several strategies that could be used to inhibit IGF action. Inhibition of receptor function by lowering protein expression, decreasing kinase activity by small-molecule inhibitors, disrupting receptor function by monoclonal antibody blockade and neutralising circulating ligand all represent potential therapeutic strategies. As these strategies move forward to clinical trial, several important considerations need to be incorporated into the clinical trial design.
KW - Cancer
KW - IGF-1
KW - IGF-1R
KW - IGF-2
KW - IGFBPs
KW - Insulin
KW - Insulin receptor
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U2 - 10.1517/13543784.13.12.1569
DO - 10.1517/13543784.13.12.1569
M3 - Review article
C2 - 15566314
AN - SCOPUS:10344222098
SN - 1354-3784
VL - 13
SP - 1569
EP - 1577
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 12
ER -